Mirabegron is a beta-3 adrenergic receptor (beta-3 AR) agonist indicated for the treatment of adult patients with overactive bladder (OAB) with symptoms of urge urinary incontinence, urgency, and urinary frequency, either as monotherapy or as combination therapy with solifenacin, a bladder-specific antimuscarinic agent. It's indicated for neurogenic detrusor overactivity (NDO) in pediatric patients 3 years and older. By relaxing the detrusor muscle via beta-3 AR activation, bladder capacity is increased during the urine storage phase. In monotherapy clinical studies for OAB, mirabegron was associated with a reduction in urinary frequency and incontinence during a 24-hour period. At the 50 mg/day dose, patients also expelled a greater volume of urine, demonstrating effectiveness at improving bladder capacity. Trials with the combined therapy of mirabegron plus solifenacin provided improvement in the number of incontinent episodes vs. solifenacin alone with similar tolerability; dry mouth and constipation were the primary side effects. Beta-3 ARs are usually well-tolerated by patients and offer an alternative for patients experiencing intolerance to selective bladder antimuscarinics. Per guidelines for non-neurogenic OAB, either bladder-specific antimuscarinics or beta-3 ARs may be used as a second-line to behavioral interventions. Clinicians may consider combination therapy with an antimuscarinic and beta-3 AR for patients refractory to monotherapy with either an antimuscarinic or beta-3 AR alone. Mirabegron therapy has the potential for increasing blood pressure and use is not recommended for those patients with severe uncontrolled hypertension (Adults, systolic blood pressure (SBP) 180 mmHg or more or diastolic blood pressure (DBP) 110 mmHg or more; Pediatrics, SBP and/or DBP above the 99th percentile plus 5 mmHg for age, sex, and stature).
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-If a dose is missed, administer it as soon as possible unless more than 12 hours have passed. If 12 hours have passed, skip the missed dose and take the next dose at the usual time.
-Mirabegron extended-release tablets and extended-release oral suspension are not substitutable on a mg-per-mg basis. Do not combine extended-release tablets and extended-release oral suspension to achieve the total dose.
Oral Solid Formulations
Extended-release tablets
-Adult patients: administer with or without food.
-Pediatric patients: administer with food.
-Swallow whole with water. Do not crush, chew, or divide.
Oral Liquid Formulations
Extended-release oral suspension (8 mg/mL after reconstitution)
-Discard the pouch and desiccant; tap the closed bottle several times to loosen the granules.
-Add 100 mL of water to the bottle and shake vigorously for 1 minute. Let stand for 10 to 30 minutes and then shake vigorously again for 1 minute. If granules have not dispersed, shake again for 1 minute.
-Take with food.
-Storage: Store reconstituted suspension at 20 to 25 degrees C (68 to 77 degrees F) for up to 28 days; discard unused portion after 28 days.
Mirabegron has been associated with clinically significant elevations in blood pressure. During treatment, monitor blood pressure periodically, particularly in patients with pre-existing high blood pressure. In clinical trials and safety studies, the following cardiovascular related adverse events were reported in adult patients receiving mirabegron monotherapy at rates higher than with placebo: hypertension (7.5% to 11.3%) and sinus tachycardia (1.2% to 1.6%). Increased blood pressure due to mirabegron was more common in those patients with baseline hypertension. In a study of pediatric patients (n = 86), 24% of patients younger than 12 years of age who were normotensive at baseline had at least 1 blood pressure measurement at or above the 95th percentile for age, sex, and stature. Stage 1 hypertension (repeated blood pressure measurements at or above the 95th percentile for age, sex, and stature) was sustained in 6 of the 10 patients (60%) at the end of the study. Palpitations were reported by less than 1% of adult patients receiving mirabegron. Both hypertension and tachycardia were listed among events most often leading to treatment discontinuation. Approximately 0.5% of adult patients discontinued the drug due to increased blood pressure. Atrial fibrillation (0.2%) was reported as a serious adverse event by more than 1 adult patient and at a rate greater than placebo. Serious adverse events reported by at least 2 adult patients receiving mirabegron and exceeding active control included stroke (cerebrovascular accident) (0.4%). In studies of adult patients treated with combination therapy with mirabegron and solifenacin, tachycardia was reported in 0.9% to 2.2% of patients.
The following gastrointestinal (GI) related adverse events were reported more frequently in adult patients receiving mirabegron relative to placebo: constipation (1.6%), diarrhea (1.2% to 1.5%), and abdominal pain (0.6% to 1.4%). Constipation (4.7%), nausea (2.3%), and gastroenteritis (2.3%) were reported in pediatric patients receiving mirabegron in an open label clinical trial (n = 86). Dyspepsia, gastritis, nausea, and abdominal distension were also reported by less than 1% of adult patients receiving mirabegron. In a separate safety study vs. active control, 2.8% of adult patients receiving mirabegron reported constipation vs. 2.7% with active control, and xerostomia was reported less often by mirabegron-treated adult patients (2.8%) vs. 8.6% for active control. Nausea, diarrhea, and constipation may lead to mirabegron discontinuation in some patients and have been reported postmarketing. Elevated hepatic enzymes (GGT increased, AST increased, ALT increased, LDH increased) have been reported by less than 1% of adult patients receiving mirabegron monotherapy. Serum ALT/AST increased from baseline by greater than 10-fold in 2 adult patients taking mirabegron 50 mg, and these markers subsequently returned to baseline while both patients continued mirabegron. In a separate clinical study in Japan, increased serum ALT, AST, and bilirubin were observed in an adult patient taking mirabegron 100 mg as well as a herbal medication (Kyufu Gold). In studies of adult patients treated with combination therapy with mirabegron and solifenacin, xerostomia (6.1% to 9.3%), constipation (3.3% to 4.2%), and dyspepsia (1.1% to 1.3%) were reported. During the co-administration trials, xerostomia led to discontinuation in 0.2% or less of adult patients.
Genitourinary related adverse events that have occurred with mirabegron in adults at the following rates and more often than with placebo include urinary tract infection (UTI) (2.9% to 4.2%). UTI (24.4%) was reported in pediatric patients receiving mirabegron in an open label clinical trial (n = 86). In addition, nephrolithiasis, bladder discomfort (pain), vaginal irritation (vulvovaginal pruritis or vaginitis), and vaginal infection were each reported by less than 1% of adult patients receiving mirabegron monotherapy. In a separate safety study, adult patients receiving mirabegron reported the following side effects relative to an active control: UTI (5.9% vs. 6.4%) and cystitis (2.1% vs. 2.3%). Overall, UTI was listed among the most commonly reported adverse reactions across the studies and was among the most common events leading to treatment discontinuation. In addition, urinary retention has been reported during postmarketing surveillance with mirabegron. In studies of adult patients treated with combination therapy with mirabegron and solifenacin, UTI was reported in 4% to 8.4% of patients. In the co-administration trials, urinary retention led to discontinuation in 0.2% or less of patients.
Adults patients receiving mirabegron monotherapy reported the following nervous system related adverse events at a higher incidence relative to placebo: headache (2.1% to 3.2%). Headache (3.5%) was reported in pediatric patients receiving mirabegron in an open label clinical trial (n = 86). In a separate safety study, adult patients receiving mirabegron reported headache (4.1% vs. 2.5%) and dizziness (2.7% vs. 2.6%) relative to an active control. Overall, headache was listed among the most commonly reported adverse reactions across the studies. Both headache and dizziness were listed among events most often leading to treatment discontinuation and have been reported with postmarketing use. In adult studies of patients treated with combination therapy with mirabegron and solifenacin, headache (2.9%) and dizziness (0.4% to 1.3%) were reported. Confusion, hallucinations, insomnia and anxiety have been reported in patients during postmarketing experience with mirabegron; the majority of these patients had pre-existing medical conditions or concomitant medications that may cause confusion, hallucinations, insomnia, and anxiety. A causal relationship between mirabegron and these disorders has not been established.
Adult patients receiving mirabegron reported the following respiratory related adverse events at rates higher than with placebo: naso-pharyngitis (3.5% to 3.9%) and upper respiratory tract infection (1.5% to 2.1%). Naso-pharyngitis (5.8%), rhinitis (2.3%), and cough (2.3%) were reported in pediatric patients receiving mirabegron in an open label clinical trial (n = 86). Sinusitis and rhinitis were reported by less than 1% of adult patients receiving mirabegron monotherapy. In a separate safety study, adult patients receiving mirabegron also reported naso-pharyngitis (3.9% vs. 3.1%), sinusitis (2.7% vs. 1.5%), and influenza (2.6% vs. 3.4%) versus an active control. Overall, naso-pharyngitis was listed among the most commonly reported respiratory adverse reactions across the studies.
Adult patients receiving mirabegron monotherapy reported the following musculoskeletal adverse events at higher rates relative to placebo: arthralgia (1.3% to 1.6%) and fatigue (1.2% to 1.4%). In a separate safety study, patients receiving mirabegron also reported back pain (2.8% vs. 1.6%) and arthralgia (2.1% vs. 2%) relative to an active control. Serious adverse events reported by at least 2 patients and exceeding active control included osteoarthritis (0.2%). In studies of patients treated with combination therapy with mirabegron and solifenacin, arthralgia was reported in 0.5% to 1.1% of patients.
In clinical evaluation, mirabegron (100 mg PO once daily) did not increase intraocular pressure in healthy adult subjects after 56 days of treatment. Nevertheless, glaucoma (ocular hypertension) was reported by less than 1% of adult patients receiving mirabegron monotherapy in safety studies. Xerophthalmia and blurred vision were listed among events most often leading to treatment discontinuation. In adult studies of patients treated with combination therapy with mirabegron and solifenacin, blurred vision was reported in 0.7% to 1.1% of patients.
Angioedema of the face, lips, tongue, and larynx, with or without respiratory symptoms, has been reported during mirabegron administration, occurring hours after the first dose or after multiple doses. Angioedema associated with upper airway swelling may be life-threatening. If involvement of the tongue, hypopharynx, or larynx occurs, mirabegron should be immediately discontinued and appropriate measures should be implemented for symptomatic treatment and ensuring a patent airway. Other dermatological and allergic adverse events reported in less than 1% of adult patients receiving mirabegron in clinical trials include urticaria, leukocytoclastic vasculitis, rash, pruritus, and purpura. In a clinical study in Japan, a single case of Stevens-Johnson syndrome was reported in an adult patient taking mirabegron 100 mg; however, the patient was also taking an herbal medication (Kyufu Gold).
Cases of new primary malignancy were reported in adult patients receiving mirabegron in clinical studies. In 3 safety studies (n = 2,736), prostate cancer (0.1%) was reported as a serious adverse event by more than 1 patient and at a rate greater than placebo. In a separate study (n = 1,624), neoplasms were reported by 0.1%, 1.3%, and 0.5% of patients treated with mirabegron 50 mg, 100 mg and active control once daily, respectively. Neoplasms reported by 2 patients treated with mirabegron 100 mg included breast cancer, malignant lung cancer, and prostate cancer. In a study of 1,206 patients receiving combination therapy with mirabegron and solifenacin, neoplasms reported by more than 1 patient included basal cell carcinoma (n = 3), breast cancer (n = 2), melanoma (n = 2), and squamous cell carcinoma (n = 2). A causal relationship between mirabegron and/or solifenacin and these reported neoplasms has not been established.
Mirabegron can increase blood pressure in pediatric and adult patients. It is not recommended for use in patients with severe uncontrolled hypertension (defined as systolic blood pressure greater than or equal to 180 mmHg and/or diastolic blood pressure greater than or equal to 110 mmHg in adults and systolic and/or diastolic blood pressure above the 99th percentile plus 5 mmHg for age, sex, and stature in pediatric patients). Monitor patients blood pressure periodically during therapy, especially in hypertensive patients. In a clinical evaluation with healthy volunteers, a dose of 50 mg/day was associated with a mean maximum increase in systolic/diastolic blood pressure of approximately 3.5/1.5 mmHg greater than placebo. In patients with overactive bladder, the mean increase in systolic and diastolic blood pressure was approximately 0.5 to 1 mmHg greater than placebo. In pediatric patients, blood pressure increases may be larger in children (3 to 11 years of age) than in adolescents (12 to 17 years of age). In a clinical study, mean increase in systolic/diastolic blood pressure of approximately 4.3/1.7 mmHg (patients younger than 12 years of age) and 5.9/2.3 mmHg (patients younger than 8 years of age) were reported in pediatric patients at a dose equivalent to 50 mg/day in adults.
Mirabegron should be administered with caution in patients with clinically significant bladder outlet obstruction (BOO), urinary tract obstruction, or with risk factors for bladder obstruction or urinary retention. In postmarketing experience, urinary retention in patients with BOO and in patients taking concomitant antimuscarinic medications for the treatment of over active bladder (OAB) has been reported. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in patients receiving mirabegron alone. The concomitant use of antimuscarinic medications or other anticholinergic medications with mirabegron in the treatment of OAB warrants caution due to the risk for urinary retention. Monitor these patients for signs and symptoms of urinary retention.
Mirabegron has not been evaluated in patients with end stage renal disease (CrCl less than 15 mL/minute), or in renal failure patients requiring dialysis; thus, it is not recommended for use in these populations. Use caution and adjust dosage in patients with severe renal impairment (CrCl 15 to 29 mL/minute). No dose adjustment is necessary in patients with mild or moderate renal impairment (CrCl 30 mL/minute or more).
Mirabegron has not been evaluated in patients with severe hepatic disease (Child-Pugh Class C) and is not recommended for use in this population. Cautious use and dosage reduction are recommended for patients with moderate hepatic impairment (Child-Pugh Class B). No dose adjustment is necessary in patients with mild hepatic impairment (Child-Pugh Class A).
Angioedema of the face, lips, tongue and/or larynx has been reported with mirabegron. Do not use mirabegron if the patient has a history of angioedema to the drug or if hypersensitivity reactions to mirabegron or tablet components have occurred.
There are no adequate and well-controlled studies of the use of mirabegron during human pregnancy to inform drug-associated risk for birth defects or miscarriage. Mirabegron administration to pregnant animals during organogenesis resulted in reversible skeletal variations (in rats) at 22-fold (via AUC) the maximum recommended human dose (MRHD) of 50 mg/day and decreased fetal body weights (in rabbits) at 14-fold the MRHD. At maternally toxic exposures in rats (96-fold), decreased fetal weight and increased fetal mortality were observed and, in rabbits (36-fold), cardiac findings (fetal cardiomegaly and fetal dilated aortae) were observed. Women who become pregnant during mirabegron treatment are encouraged to contact their physician.
Use mirabegron with caution during breast-feeding. There is no information regarding the presence of mirabegron in human milk, the effects on the breast-fed child, or the effects on milk production. Mirabegron-related material was present in rat milk and in the stomach of nursing pups following administrations of a single 10 mg/kg oral dose of radiolabeled mirabegron to lactating rats. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). According to the OBRA guidelines, assessment of the underlying causes and identification of the type/category of urinary incontinence needs to be documented prior to or soon after the time of initiating treatment with a urinary incontinence medication such as mirabegron. These medications have specific and limited indications based on the cause and categorization of incontinence. Patients should be assessed periodically for medication effects on urinary incontinence as well as lower urinary tract symptoms and treatment tolerability.
General Dosing Information
-Mirabegron extended-release tablets and mirabegron extended-release oral suspension are not substitutable on a mg-per-mg basis. Do not combine extended-release tablets and extended-release oral suspension to achieve the total dose.
For the treatment of overactive bladder (OAB) with symptoms of urge urinary incontinence, urinary urgency, and urinary frequency:
Oral dosage (extended-release tablets):
Adults: 25 mg PO once daily, initially. May increase the dose to 50 mg PO once daily after 4 to 8 weeks if needed.
For the treatment of neurogenic detrusor overactivity (neurogenic bladder):
Oral dosage (extended-release oral suspension):
Children and Adolescents 3 to 17 years weighing 35 kg or more: 48 mg PO once daily. May increase dose to 80 mg PO once daily after 4 to 8 weeks if needed.
Children and Adolescents 3 to 17 years weighing 22 to 34 kg: 32 mg PO once daily initially. May increase dose to 64 mg PO once daily after 4 to 8 weeks if needed. Evaluate patients periodically for potential dosage adjustments based on weight.
Children and Adolescents 3 to 17 years weighing 11 to 21 kg: 24 mg PO once daily. May increase dose to 48 mg PO once daily after 4 to 8 weeks if needed. Evaluate patients periodically for potential dosage adjustments based on weight.
Oral dosage (extended-release tablets):
Children and Adolescents 3 to 17 years weighing 35 kg or more: 25 mg PO once daily. May increase dose to 50 mg PO once daily after 4 to 8 weeks if needed.
Maximum Dosage Limits:
-Adults
50 mg/day PO for the extended-release tablets; safety and efficacy have not been established for the extended-release oral suspension.
-Geriatric
50 mg/day PO for the extended-release tablets; safety and efficacy have not been established for the extended-release oral suspension.
-Adolescents
weighing 35 kg or more: 80 mg/day PO for the extended-release oral suspension; 50 mg/day PO for the extended-release tablets.
weighing 22 to 34 kg: 64 mg/day PO for the extended-release oral suspension; safety and efficacy have not been established for the extended-release tablets.
weighing 11 to 21 kg: 48 mg/day PO for the extended-release oral suspension; safety and efficacy have not been established for the extended-release tablets.
-Children
3 to 12 years weighing 35 kg or more: 80 mg/day PO for the extended-release oral suspension; 50 mg/day PO for the extended-release tablets.
3 to 12 years weighing 22 to 34 kg: 64 mg/day PO for the extended-release oral suspension; safety and efficacy have not been established for the extended-release tablets.
3 to 12 years weighing 11 to 21 kg: 48 mg/day PO for the extended-release oral suspension; safety and efficacy have not been established for the extended-release tablets.
1 to 2 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Extended-release tablet
Mild hepatic impairment (Child Pugh Class A): No dosage adjustment needed.
Moderate hepatic impairment (Child Pugh Class B): Do not exceed 25 mg once daily.
Severe hepatic impairment (Child Pugh Class C): Not recommended.
Extended-release oral suspension
Mild hepatic impairment (Child Pugh Class A): No dosage adjustment needed.
Moderate hepatic impairment (Child Pugh Class B):
-Patients weighing 11 to 21 kg: Do not exceed 24 mg once daily.
-Patients weighing 22 to 34 kg: Do not exceed 32 mg once daily.
-Patients weighing 35 kg or more: Do not exceed 48 mg once daily.
Severe hepatic impairment (Child Pugh Class C): Not recommended.
Patients with Renal Impairment Dosing
Extended-release tablet
eGFR 30 mL/minute/1.73 m2 or more: No dosage adjustment needed.
eGFR 15 to 29 mL/minute/1.73 m2: Do not exceed 25 mg once daily.
eGFR less than 15 mL/minute/1.73 m2: Not recommended.
Extended-release oral suspension
eGFR 30 mL/minute/1.73 m2 or more: No dosage adjustment needed.
eGFR 15 to 29 mL/minute/1.73 m2:
-Patients weighing 11 to 21 kg: Do not exceed 24 mg once daily.
-Patients weighing 22 to 34 kg: Do not exceed 32 mg once daily.
-Patients weighing 35 kg or more: Do not exceed 48 mg once daily.
eGFR less than 15 mL/minute/1.73 m2: Not recommended.
Intermittent hemodialysis
Not recommended in patients with end-stage renal disease (ESRD) or patients on dialysis.
*non-FDA-approved indication
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with mirabegron may increase dihydrocodeine plasma concentrations, but decrease the plasma concentration of the active metabolite, dihydromorphine, resulting in reduced efficacy or symptoms of opioid withdrawal. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of dihydrocodeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease dihydrocodeine plasma concentrations and increase dihydromorphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Dihydrocodeine is primarily metabolized by CYP2D6 to dihydromorphine, and by CYP3A4. Mirabegron is a moderate inhibitor of CYP2D6.
Acetaminophen; Chlorpheniramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Acetaminophen; Dextromethorphan: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Doxylamine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Phenylephrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Acetaminophen; Diphenhydramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6.
Amitriptyline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Amoxapine: (Major) Concomitant use of amoxapine with drugs that can inhibit cytochrome P450 2D6, such as mirabegron, may require lower doses than usually prescribed for either amoxapine or mirabegron. Furthermore, whenever mirabegron is withdrawn from co-therapy, an increased dose of the amoxapine may be required. It is desirable to monitor amoxapine plasma levels whenever amoxapine is going to be co-administered with another drug known to be an inhibitor of P450 2D6.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of mirabegron. Patients receiving both a CYP3A inhibitor plus mirabegron may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form and CYP3A inhibitor strength. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP2D6 and CYP3A substrate; mirabegron is a moderate CYP2D6 inhibitor.
Asenapine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as asenapine may be increased when co-administered with mirabegron. Asenapine has been shown to be a CYP2D6 substrate in vitro. Appropriate monitoring and dose adjustment may be necessary.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Atazanavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Atomoxetine: (Moderate) Because atomoxetine is primarily metabolized by CYP2D6, concurrent use of CYP2D6 inhibitors such as mirabegron may theoretically increase the risk of atomoxetine-induced adverse effects. Monitor for adverse effects, such as dizziness, drowsiness, nervousness, insomnia, and cardiac effects (e.g., hypertension, QT prolongation).
Brimonidine; Timolol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as timolol may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Brompheniramine; Dextromethorphan; Phenylephrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Carvedilol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as carvedilol may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Celecoxib; Tramadol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tramadol may be increased when co-administered with mirabegron. Tramadol is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlordiazepoxide; Amitriptyline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Dextromethorphan: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Chlorpheniramine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpheniramine; Pseudoephedrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpheniramine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Chlorpromazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as chlorpromazine may be increased when co-administered with mirabegron. Chlorpromazine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Clomipramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Clozapine: (Moderate) Patients receiving clozapine in combination with a CYP2D6 inhibitor such as mirabegron should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary. Mirabegron is a moderate inhibitor of CYP2D6, and clozapine is a CYP2D6 substrate. Elevated plasma concentrations of clozapine may potentially increase the risk of life-threatening arrhythmias, sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects.
Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Codeine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as promethazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with mirabegron may increase codeine plasma concentrations, but decrease the plasma concentration of the active metabolite, morphine, resulting in reduced efficacy or symptoms of opioid withdrawal. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage increase of codeine until stable drug effects are achieved. Discontinuation of mirabegron could decrease codeine plasma concentrations and increase morphine plasma concentrations resulting in prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If mirabegron is discontinued, monitor the patient carefully and consider reducing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mirabegron is a moderate inhibitor of CYP2D6. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as promethazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Darifenacin: (Moderate) Mirabegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as darifenacin, because of the risk of urinary retention. In addition, mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as darifenacin may be increased when administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Delavirdine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as delavirdine may be increased when administered with mirabegron. Delavirdine has been shown to be a CYP2D6 substrate invitro. Appropriate monitoring and dose adjustment may be necessary.
Desipramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Bupropion: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Guaifenesin: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Guaifenesin; Phenylephrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Dextromethorphan; Quinidine: (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Digoxin: (Major) Mirabegron increases digoxin exposure approximately 30% with concomitant use. Measure serum digoxin concentrations prior to initiating mirabegron. Reduce the digoxin dose by approximately 15% to 30% or modify the dosing frequency when given together. Monitor digoxin concentrations and titrate the dose to obtain the desired clinical effect.
Diphenhydramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Diphenhydramine; Ibuprofen: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Diphenhydramine; Naproxen: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Diphenhydramine; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as diphenhydramine may be increased when co-administered with mirabegron. Diphenhydramine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Dolasetron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as dolasetron may be increased when co-administered with mirabegron. Dolasetron is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Donepezil: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as donepezil may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Donepezil; Memantine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as donepezil may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Dorzolamide; Timolol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as timolol may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Doxepin: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Doxorubicin Liposomal: (Major) Mirabegron is a moderate CYP2D6 inhibitor; doxorubicin is a substrate of both CYP2D6 and CYP3A4. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of mirabegron and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Major) Mirabegron is a moderate CYP2D6 inhibitor; doxorubicin is a substrate of both CYP2D6 and CYP3A4. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP2D6, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of mirabegron and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Duloxetine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as duloxetine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Dutasteride; Tamsulosin: (Moderate) The effect of mirabegron on tamsulosin pharmacokinetics was determined in drug interaction studies, there was a lack of pharmacokinetic interaction. However, it is recommended that mirabegron be administered with caution in patients taking other medications in the setting of risks for urinary obstruction because of the risk of urinary retention. This includes caution when used with tamsulosin. In addition, mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as tamsulosin may be increased when co-administered with mirabegron.
Eliglustat: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of mirabegron and eliglustat is not recommended. In extensive or intermediate CYP2D6 metabolizers (EMs or IMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both mirabegron and a moderate or strong CYP3A inhibitor is contraindicated in all patients. Mirabegron is a moderate CYP2D6 inhibitor; eliglustat is a CYP2D6 and CYP3A substrate. Coadministration of eliglustat with CYP2D6 inhibitors, such as mirabegron, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with mirabegron as there is a potential for elevated cobicistat concentrations. Mirabegron is a moderate CYP2D6 inhibitor. Cobicistat is a substrate of CYP2D6 and CYP3A4.
Fesoterodine: (Moderate) Mirabegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as fesoterodine, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these medicines together.
Flecainide: (Major) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as flecainide may be increased when administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Fluoxetine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as fluoxetine may be increased when co-administered with mirabegron. Fluoxetine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Fluphenazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as fluphenazine may be increased when co-administered with mirabegron. Fluphenazine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as umeclidinium may be increased when co-administered with mirabegron. Umeclidinium is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. Monitor for dry mouth, constipation, blurred vision or urinary retention.
Fluvoxamine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as fluvoxamine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Fosamprenavir: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as fosamprenavir may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with mirabegron is necessary; the risk is increased in CYP2D6 poor metabolizers. Based on in vitro data, gefitinib is metabolized to O-desmethyl gefitinib by CYP2D6 and mirabegron is a CYP2D6 inhibitor. In healthy CYP2D6 poor metabolizers, the concentration of O-desmethyl gefitinib was not measurable and mean exposure to gefitinib was 2-fold higher compared to extensive metabolizers. The impact of CYP2D6 inhibitors on gefitinib pharmacokinetics has not been evaluated; however, the manufacturer recommends precautions based on exposure in patients with poor CYP2D6 metabolism.
Haloperidol: (Moderate) Mirabegron is a substrate and a moderate inhibitor of CYP2D6. Exposure of drugs metabolized by CYP2D6 such as haloperidol may be increased when co-administered with mirabegron. Haloperidol is primarily metabolized by CYP2D6. In addition, in vitro data suggest that haloperidol has CYP2D6 inhibitory effects and has the potential to decrease the metabolism of CYP2D6 substrates such as mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Homatropine; Hydrocodone: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6.
Hydrocodone: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of hydrocodone with mirabegron may increase hydrocodone plasma concentrations and prolong opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when hydrocodone is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of hydrocodone until stable drug effects are achieved. Discontinuation of mirabegron could decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to hydrocodone. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Hydrocodone is a substrate for CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6.
Iloperidone: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as iloperidone may be increased whenadministered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Imipramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Indacaterol; Glycopyrrolate: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as indacaterol may be increased when administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Isocarboxazid: (Moderate) It is unclear if it is safe to use of mirabegron with MAOI therapy. It may be best to use caution and avoid use together if possible. Use of mirabegron (a selective beta-3 adrenergic agonist) with non-selective MAOIs may theoretically result in an increased risk for high blood pressure. Mirabegron has increased blood pressure at clinically used doses (e.g., 50 mg/day). In these studies, at the maximum recommended dose of 50 mg/day, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mmHg greater than placebo. Beta-3 selectivity is usually lost at doses above those used clinically for overactive bladder (e.g, 200 mg/day PO). Sympathomimetic adrenergic agonists are typically contraindicated in patients receiving MAOIs. When administering a MAOI in close proximity to such a drug, at least 2 weeks should usually elapse between discontinuation of 1 agent and initiation of therapy with the other; consult the specific product literature for precise recommendations.
Ivermectin: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as ivermectin may be increased when co-administered with mirabegron. Ivermectin has been shown to be a CYP2D6 substrate in vitro. Appropriate monitoring and dose adjustment may be necessary.
Lopinavir; Ritonavir: (Moderate) Concurrent administration of mirabegron with ritonavir may result in elevated plasma concentrations of ritonavir. Mirabegron is a moderate inhibitor of CYP2D6. Ritonavir is a CYP2D6 substrate. Caution and close monitoring are advised if these drugs are administered together.
Maprotiline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as maprotiline may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Meclizine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as meclizine may be increased when co-administered with mirabegron. Meclizine has been shown to be a CYP2D6 substrate in vitro. Appropriate monitoring and dose adjustment may be necessary.
Methadone: (Moderate) Concurrent use of methadone with mirabegron may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Monitor closely until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Methadone is a substrate for CYP3A4 and CYP2D6. Mirabegron is a moderate inhibitor of CYP2D6. Discontinuation of mirabegron in a patient taking methadone chronically may decrease methadone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If mirabegron is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate.
Metoprolol: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; mirabegron is a moderate CYP2D6 inhibitor. In drug interaction studies, mirabegron increased the Cmax and AUC of metoprolol by 90% and 229%, respectively, after multiple doses of 160 mg mirabegron IR tablets once daily for 5 days and a single dose of 100 mg metoprolol tablet administered before and concomitantly with mirabegron.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for increased metoprolol adverse reactions including bradycardia and hypotension during coadministration. A dosage reduction for metoprolol may be needed based on response. Concurrent use may increase metoprolol exposure. Metoprolol is a CYP2D6 substrate; mirabegron is a moderate CYP2D6 inhibitor. In drug interaction studies, mirabegron increased the Cmax and AUC of metoprolol by 90% and 229%, respectively, after multiple doses of 160 mg mirabegron IR tablets once daily for 5 days and a single dose of 100 mg metoprolol tablet administered before and concomitantly with mirabegron.
Mexiletine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as mexiletine may be increased when co-administered with mirabegron. Mexiletine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Mirtazapine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs partially metabolized by CYP2D6 such as mirtazapine may be increased when co-administered with mirabegron. Mirtazapine as a substrate for several CYP450 isoenzymes including 2D6, 1A2, and 3A4 in vitro. Appropriate monitoring and dose adjustment may be necessary.
Monoamine oxidase inhibitors: (Moderate) It is unclear if it is safe to use of mirabegron with MAOI therapy. It may be best to use caution and avoid use together if possible. Use of mirabegron (a selective beta-3 adrenergic agonist) with non-selective MAOIs may theoretically result in an increased risk for high blood pressure. Mirabegron has increased blood pressure at clinically used doses (e.g., 50 mg/day). In these studies, at the maximum recommended dose of 50 mg/day, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mmHg greater than placebo. Beta-3 selectivity is usually lost at doses above those used clinically for overactive bladder (e.g, 200 mg/day PO). Sympathomimetic adrenergic agonists are typically contraindicated in patients receiving MAOIs. When administering a MAOI in close proximity to such a drug, at least 2 weeks should usually elapse between discontinuation of 1 agent and initiation of therapy with the other; consult the specific product literature for precise recommendations.
Nebivolol: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with mirabegron. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as mirabegron, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. Dose adjustment may be necessary.
Nebivolol; Valsartan: (Moderate) Monitor for increased toxicity as well as increased therapeutic effect of nebivolol if coadministered with mirabegron. Nebivolol is metabolized by CYP2D6. Although data are lacking, CYP2D6 inhibitors, such as mirabegron, could potentially increase nebivolol plasma concentrations via CYP2D6 inhibition; the clinical significance of this potential interaction is unknown, but an increase in adverse effects is possible. Dose adjustment may be necessary.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as palonosetron may be increased when co-administered with mirabegron. Palonosetron is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Nirmatrelvir; Ritonavir: (Moderate) Concurrent administration of mirabegron with ritonavir may result in elevated plasma concentrations of ritonavir. Mirabegron is a moderate inhibitor of CYP2D6. Ritonavir is a CYP2D6 substrate. Caution and close monitoring are advised if these drugs are administered together.
Nortriptyline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Olanzapine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as olanzapine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Olanzapine; Fluoxetine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as fluoxetine may be increased when co-administered with mirabegron. Fluoxetine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as olanzapine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Olanzapine; Samidorphan: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as olanzapine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and mirabegron is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and mirabegron may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If mirabegron is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP2D6 substrate and mirabegron is a moderate CYP2D6 inhibitor.
Ondansetron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs partially metabolized by CYP2D6, such as ondansetron may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Oxybutynin: (Moderate) Mirabegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as oxybutynin, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Palonosetron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as palonosetron may be increased when co-administered with mirabegron. Palonosetron is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Paroxetine: (Moderate) Monitor for an increase in paroxetine-related adverse reactions, including serotonin syndrome, if concomitant use with mirabegron is necessary. Concomitant use may increase paroxetine exposure. Paroxetine is a CYP2D6 substrate and mirabegron is a moderate CYP2D6 inhibitor.
Pentamidine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as systemic pentamidine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Perphenazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as perphenazine may be increased when co-administered with mirabegron. Perphenazine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Perphenazine; Amitriptyline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as perphenazine may be increased when co-administered with mirabegron. Perphenazine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Phenelzine: (Moderate) It is unclear if it is safe to use of mirabegron with MAOI therapy. It may be best to use caution and avoid use together if possible. Use of mirabegron (a selective beta-3 adrenergic agonist) with non-selective MAOIs may theoretically result in an increased risk for high blood pressure. Mirabegron has increased blood pressure at clinically used doses (e.g., 50 mg/day). In these studies, at the maximum recommended dose of 50 mg/day, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mmHg greater than placebo. Beta-3 selectivity is usually lost at doses above those used clinically for overactive bladder (e.g, 200 mg/day PO). Sympathomimetic adrenergic agonists are typically contraindicated in patients receiving MAOIs. When administering a MAOI in close proximity to such a drug, at least 2 weeks should usually elapse between discontinuation of 1 agent and initiation of therapy with the other; consult the specific product literature for precise recommendations.
Pimozide: (Moderate) Caution is advisable during concurrent use of pimozide and moderate CYP2D6 inhibitors such as mirabegron. Pimozide is metabolized primarily through CYP3A4, and to a lesser extent CYP1A2 and CYP2D6. While the manufacturer has provided no guidance regarding pimozide use with mild or moderate CYP2D6 inhibitors, concurrent use of the drug with more potent inhibitors of CYP2D6 is contraindicated. Elevated concentrations of pimozide can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Pirfenidone: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as pirfenidone may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Promethazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as promethazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Promethazine; Dextromethorphan: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as promethazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary. (Minor) Use of dextromethorphan with mirabegron may result in increased dextromethorphan exposure. Mirabegron moderately inhibits CYP2D6 and dextromethorphan is a CYP2D6 substrate. Monitor for dextromethorphan-related side effects, such as drowsiness, nausea or vomiting, sweating, restlessness, or tremor.
Promethazine; Phenylephrine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as promethazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Propafenone: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as propafenone may be increased when administered with mirabegron. This is especially true for patients who are also CYP2D6 poor metabolizers (PMs). Therefore, appropriate monitoring and dose adjustment may be necessary.
Propranolol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as propranolol may be increased when co-administered with mirabegron. Propranolol is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Protriptyline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Quinine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as quinine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Ranolazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as ranolazine may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Ritonavir: (Moderate) Concurrent administration of mirabegron with ritonavir may result in elevated plasma concentrations of ritonavir. Mirabegron is a moderate inhibitor of CYP2D6. Ritonavir is a CYP2D6 substrate. Caution and close monitoring are advised if these drugs are administered together.
Sertraline: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as sertraline may be increased when co-administered with mirabegron. Sertraline has been shown to be a CYP2D6 substrate and a mild to moderate inhibitor of CYP2D6 in vitro. Mirabegron exposure may also increase. Appropriate monitoring and dose adjustment may be necessary.
Solifenacin: (Moderate) Limit the solifenacin dose to 5 mg/day when used in combination mirabegron, and monitor for signs and symptoms of urinary retention.
Tamsulosin: (Moderate) The effect of mirabegron on tamsulosin pharmacokinetics was determined in drug interaction studies, there was a lack of pharmacokinetic interaction. However, it is recommended that mirabegron be administered with caution in patients taking other medications in the setting of risks for urinary obstruction because of the risk of urinary retention. This includes caution when used with tamsulosin. In addition, mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as tamsulosin may be increased when co-administered with mirabegron.
Tetrabenazine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tetrabenazine may be increased when administered with mirabegron. Two of the primary metabolites of tetrabenazine, alpha-dihydrotetrabenzaine (alpha-HTBZ) and beta-dihydrotetrabenazine (beta-HTBZ), are substrates for CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Thioridazine: (Contraindicated) Mirabegron is a moderate inhibitor of CYP2D6 and the use of thioridazine concomitantly with CYP2D6 inhibitors is contraindicated due to the possible risk of QT prolongation and subsequent arrhythmias, or other serious side effects, due to elevated serum concentrations of thioridazine.
Timolol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as timolol may be increased when co-administered with mirabegron. Therefore, appropriate monitoring and dose adjustment may be necessary.
Tolterodine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tolterodine may be increased when administered with mirabegron. Tolterodine is primarily metabolized by CYP2D6. Mirabegron should also be used with caution in patients taking antimuscarinic medications for the treatment of overactive bladder because of the risk of urinary retention. Appropriate monitoring and dose adjustment may be necessary. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Tramadol: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tramadol may be increased when co-administered with mirabegron. Tramadol is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Tramadol; Acetaminophen: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as tramadol may be increased when co-administered with mirabegron. Tramadol is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Tranylcypromine: (Moderate) It is unclear if it is safe to use of mirabegron with MAOI therapy. It may be best to use caution and avoid use together if possible. Use of mirabegron (a selective beta-3 adrenergic agonist) with non-selective MAOIs may theoretically result in an increased risk for high blood pressure. Mirabegron has increased blood pressure at clinically used doses (e.g., 50 mg/day). In these studies, at the maximum recommended dose of 50 mg/day, the mean maximum increase in systolic/diastolic blood pressure was approximately 3.5/1.5 mmHg greater than placebo. Beta-3 selectivity is usually lost at doses above those used clinically for overactive bladder (e.g, 200 mg/day PO). Sympathomimetic adrenergic agonists are typically contraindicated in patients receiving MAOIs. When administering a MAOI in close proximity to such a drug, at least 2 weeks should usually elapse between discontinuation of 1 agent and initiation of therapy with the other; consult the specific product literature for precise recommendations.
Tricyclic antidepressants: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Trimipramine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of tricyclic antidepressants (TCAs), which are CYP2D6 substrates, may be increased when co-administered with mirabegron. In drug interaction studies, mirabegron increased the Cmax of desipramine by 79% and desipramine AUC by 241% after multiple dose administration of 100 mg mirabegron once daily for 18 days and a single dose of 50 mg desipramine before and concomitantly with mirabegron. It is difficult to predict the magnitude of the interaction with each TCA due to differences in the role of CYP2D6 in the metabolism of these drugs. Therefore, appropriate monitoring and dose adjustment may be necessary.
Trospium: (Moderate) Mirabegron should be administered with caution in patients taking antimuscarinic medications for the treatment of overactive bladder, such as oxybutynin, because of the risk of urinary retention. Monitor for symptoms of urinary difficulties or urinary retention. Patients may note constipation or dry mouth with use of these drugs together.
Umeclidinium: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as umeclidinium may be increased when co-administered with mirabegron. Umeclidinium is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. Monitor for dry mouth, constipation, blurred vision or urinary retention.
Umeclidinium; Vilanterol: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as umeclidinium may be increased when co-administered with mirabegron. Umeclidinium is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary. Monitor for dry mouth, constipation, blurred vision or urinary retention.
Venlafaxine: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 such as venlafaxine may be increased when co-administered with mirabegron. Venlafaxine is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Vilazodone: (Minor) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as vilazodone may be increased when co-administered with mirabegron. However, CYP2D6 is a minor metabolic pathway for vilazodone. Appropriate monitoring may be necessary.
Warfarin: (Moderate) When given in combination, mirabegron increased the mean warfarin (S- and R-warfarin) Cmax by approximately 4% and the AUC by approximately 9% when administered as a single dose of 25 mg warfarin after multiple doses of 100 mg mirabegron. Following a single dose administration of 25 mg warfarin, mirabegron had no effect on INR and prothrombin time. However, the effect of mirabegron on multiple doses of warfarin and on warfarin pharmacodynamic end points such as INR and prothrombin time has not been fully investigated. Therefore, careful monitoring and dose adjustment may be necessary.
Mirabegron is a human beta-3 adrenergic receptor (AR) agonist. Mirabegron relaxes the detrusor smooth muscle during the storage phase of the urinary bladder fill-void cycle by activation of beta-3 AR which increases bladder capacity. Although mirabegron showed very low intrinsic activity for cloned human beta-1 AR and beta-2 AR, results in humans indicate that beta-1 AR stimulation occurred at a mirabegron dose of 200 mg.
Mirabegron is administered orally. It is extensively distributed throughout the body. Approximately 71% is bound to human plasma proteins with a moderate affinity for albumin and alpha-1 acid glycoprotein. In vitro, it distributes to erythrocytes with concentrations about 2-fold higher than in plasma. Mirabegron is metabolized via multiple pathways involving dealkylation, oxidation, (direct) glucuronidation, and amide hydrolysis. Mirabegron is the major circulating component. Two non-active metabolites were observed in human plasma and are phase 2 glucuronides representing 16% and 11% of total exposure, respectively. Although in vitro studies suggest a role for CYP2D6 and CYP3A4 in the oxidative metabolism of mirabegron, in vivo results indicate that these isozymes play a limited role in the overall elimination of the drug. Renal elimination of mirabegron is primarily through active tubular secretion along with glomerular filtration. Urinary elimination of unchanged mirabegron is dose-dependent and ranges from approximately 6% after a daily dose of 25 mg to 12.2% after a daily dose of 100 mg. In studies, 55% of radiolabeled mirabegron was recovered in the urine and 34% in the feces; approximately 25% of unchanged mirabegron was recovered in urine and 0% in feces. The terminal elimination half-life is approximately 50 hours.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6, P-gp
Mirabegron is a moderate CYP2D6 inhibitor and may reduce the elimination of other drugs dependent on this isozyme for metabolism. Because of the limited role of CYP3A4 and CYP2D6 in the overall elimination of mirabegron in vivo, drug-drug interactions with inducers or inhibitors of these 2 enzymes do not have a significant effect on mirabegron disposition and no dosage adjustments of mirabegron are needed. Involvement of butylcholinesterase, uridine diphospho-glucuronosyltransferases (UGT) and possibly alcohol dehydrogenase metabolism has been demonstrated for mirabegron. Mirabegron is also a substrate for butyrylcholinesterase, UGT, the efflux transporter P-glycoprotein (P-gp), and the influx organic cation transporters (OCT) OCT1, OCT2, and OCT3; however, clinically significant drug-drug interactions related to these drug transporters are unclear. A small effect of mirabegron on digoxin, a P-gp substrate with a narrow therapeutic index, has been noted and requires caution with concurrent use.
-Route-Specific Pharmacokinetics
Oral Route
After oral administration in adult patients, mirabegron Cmax is attained at approximately 3.5 hours. Absolute bioavailability is dose-proportional, increasing from 29% to 35% as dose increases from 25 to 50 mg; mean Cmax and AUC increase more than dose-proportionally, especially for doses greater than 50 mg. In the overall population of males and females, a 2-fold increase in dose from 50 to 100 mg increased Cmax and AUC by approximately 2.9- and 2.6-fold, respectively, whereas a 4-fold increase in dose from 50 to 200 mg increased Cmax and AUC by approximately 8.4- and 6.5-fold. There are no clinically significant differences in mirabegron pharmacokinetics when administered with or without food in adult patients. Steady state concentrations are achieved within 7 days. Plasma exposure of mirabegron at steady state is approximately double that seen after a single dose.
-Special Populations
Hepatic Impairment
After single dose administration of mirabegron (100 mg), mean Cmax and AUC were increased by 9% and 19% respectively, in subjects with mild hepatic impairment (Child-Pugh Class A) compared to subjects with normal hepatic function. In the presence of moderate hepatic impairment (Child-Pugh Class B), mean Cmax and AUC values were 175% and 65% higher. Mirabegron has not been studied in patients with severe hepatic impairment (Child-Pugh Class C).
Renal Impairment
After single dose administration of mirabegron (100 mg), mean Cmax and AUC were increased by 6% and 31% respectively, in subjects with mild renal impairment (eGFR 60 to 89 mL/minute/1.73 m2) compared to subjects with normal renal function. In the presence of moderate renal impairment (eGFR 30 to 59 mL/minute/1.73 m2), mean Cmax and AUC values were 23% and 66% higher. In subjects with severe renal impairment (eGFR 15 to 29 mL/minute/1.73 m2), mean Cmax and AUC values were 92% and 118% higher compared to subjects with normal renal function. Mirabegron has not been studied in patients with end stage renal disease (ESRD, eGFR less than 15 mL/minute/1.73 m2) or in patients in requiring hemodialysis.
Pediatrics
In pediatric patients 3 to 17 years, age was not predicted to affect mirabegron pharmacokinetic parameters after accounting for differences in body weight. The Vd of mirabegron is larger in pediatric patients (4,895 to 13,726 L) compared to adults (1,670 L), and increased with increasing body weight. The mean terminal elimination half-life in pediatric patients is approximately 26 to 31 hours, which is shorter than that observed in adults (50 hours). Predictive models have shown that mirabegron clearance in pediatric patients increased with body weight. After oral administration in pediatric patients, the median Tmax of mirabegron after administration of a single dose of extended-release tablets or extended-release oral suspension under fed conditions was 4 to 5 hours. Population pharmacokinetic analysis predicted a median Tmax of 3 to 4 hours at steady-state. Under fasted conditions, the steady-state AUC of mirabegron extended-release tablets increased by 120% relative to fed conditions in pediatric patients. Fasted Cmax and AUC of the extended-release oral suspension increased by 170% and 80%, respectively, compared to fed conditions in healthy volunteers.
Geriatric
The Cmax and AUC of mirabegron after multiple oral doses in elderly adult volunteers (65 years of age or greater) were similar to those in younger adult volunteers (18 to 45 years).
Gender Differences
The Cmax and AUC of mirabegron were approximately 40% to 50% higher in adult females than in adult males. When corrected for differences in body weight, the mirabegron systemic exposure is 20% to 30% higher in females compared to males. In pediatric patients, gender has no meaningful impact on mirabegron pharmacokinetics.
Ethnic Differences
The pharmacokinetics of mirabegron were comparable between White patients and Black patients. Cross studies comparison shows that the exposure in Japanese subjects is higher than that in North American subjects. However, when the Cmax and AUC were normalized for dose and body weight, the difference is smaller.
Other
CYP2D6 Poor Metabolizers (PMs)
In healthy subjects who were poor metabolizers of CYP2D6, the mean Cmax and AUC were approximately 16% and 17% higher than in extensive metabolizers of CYP2D6, respectively; however, these changes are not clinically significant. There is a limited role of CYP2D6 in the overall elimination of mirabegron in vivo.